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Integrin endocytosis on elastic substrates mediates mechanosensing.
Jing Li1, Huarong Chen2, Yue Xu1
1Institute of Biomechanics and Medical Engineering, School of Aerospace Engineering,Tsinghua University, Beijing 100084, PR China.
Journal of Biomechanics
|June 27, 2016
Summary
Cell integrin internalization on soft substrates promotes differentiation. Specific integrins (α1, α2) are internalized on soft collagen I, unlike others (α5, α6) on different matrices, revealing ligand-specific mechanosensing.
Area of Science:
- Biophysics
- Cell Biology
- Biomaterials Science
Background:
- Tissue mechanics influence cell behavior and function.
- Integrin proteins are key mediators of mechanosensing, linking extracellular matrix (ECM) and intracellular cytoskeleton.
- Previous studies showed integrin β1 endocytosis on soft substrates promotes bone marrow mesenchymal stem cell (BMMSC) differentiation.
Purpose of the Study:
- To investigate the role of other integrin subunits in BMMSC mechanosensing on varying substrate stiffness.
- To determine if soft substrate-induced integrin endocytosis is specific to certain integrin-ligand interactions.
Main Methods:
- Immunocytochemical staining and biotin labeling experiments were performed on BMMSCs cultured on soft and stiff hydrogels.
- Hydrogels were coated with specific ECM proteins: collagen I, fibronectin, and laminin.
- Subcellular distribution of integrin subunits was analyzed.
Main Results:
- Integrins α1 and α2 showed increased internalization on soft collagen I-coated substrates compared to stiff counterparts.
- This internalization was primarily mediated by caveolin-dependent endocytosis.
- Integrins α5 and α6 did not exhibit significant soft substrate-induced endocytosis on fibronectin or laminin coatings, respectively.
- Soft matrix-promoted neurogenic lineage commitment involves integrin internalization.
Conclusions:
- Integrin-mediated mechanosensing is coupled with specific ECM ligands.
- The internalization of integrins α1 and α2 on soft substrates is a key mechanism for sensing matrix elasticity and promoting specific cell lineage commitment.
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